912 7. MEECURIALS 



cant depression of respiration, as in the uptake of I" by Fucus, where 0.05 

 YoM p-MB inhibits transport 50% but 0.2 mM does not affect respiration 

 (Klemperer, 1957), or the accumulation of K+ by Porphyra, where p-MB 

 decreases the number of ions pumped per Og consumed (Eppley, 1960), or 

 the active transport of Na+ through frog skin, which is blocked by Hg++ 

 at a concentration not altering respiration (Linderholm, 1952). In such 

 cases it has generally been assumed that the action is on the transport 

 system itself, but this is not necessarily true. It is rather surprising that so 

 few have reported instances of decreased permeability brought about by 

 the mercurials, particularly the organic ones, inasmuch as they might be 

 expected to react with SH groups in or around the membrane pores to 

 impede the passage of substances across the membrane; perhaps this would 

 be observed more often if lower concentrations were examined. The per- 

 meability of frog skin to Cl~ is decreased by p-MB, and Janacek (1962) 

 postulated that the mercurial sterically hinders the movement of anions 

 through the pores. 



Certain results occasionally point to an effect of mercurials on the end- 

 ergonic phase of transport rather than a simple depression of ATP forma- 

 tion. The fact that Hg+^ at 0.5 mM inhibits the 20-sec uptake of acetate 

 by diaphragm without a lag period (Foulkes and Paine, 1961), taken with 

 the rather slow depression of metabolism, is indicative of an action directly 

 on the membrane. We have also seen that p-MB lyses erythrocytes without 

 reacting with intracellular glutathione or inhibiting glycolysis, in contrast 

 to A^-ethylmaleimide, and that this has been attributed to a failure to pene- 

 trate into the cells, so that the effects observed must involve an attack on 

 the membrane (Jacob and Jandl, 1962). Hg++ very potently inhibits stro- 

 mal ATPase — 50% inhibition at around 0.00125 mM, and plots of log 

 {vjvi — 1) against log (Hg++) suggest that 3 Hg++ ions are required for 

 each ATPase molecule (Laris et al., 1962). The same type of behavior was 

 observed for the inhibition of glucose uptake, and the concentrations of 

 Hg++ required to inhibit are comparable (LeFevre, 1954). Laris et al. re- 

 plotted LeFevre's data and found that roughly 6 ions of Hg++ are necessary 

 for the inhibition of the transport of each glucose molecule. The similar 

 sensitivities and kinetics allowed them to postulate that the two inhibi- 

 tions may be closely related. The stimulation of the uptake of certain sugars 

 (e.g., D-xylose and L-arabinose) into diaphragm by p-MB, and the inhibition 

 of the stimulation produced by insulin, may well be on the muscle mem- 

 branes (Kono and Colowick, 1961). There is certainly no correlation with 

 the level of ATP, and p-MB actually seems to increase ATP somewhat. A 

 block between ATP and the transport system was considered a possibility. 



The reaction of mercurials with a membrane carrier was adduced to ex- 

 plain the inhibition of phosphate transport in Micrococcus pyogenes by Hg++ 

 and PM (P. Mitchell, 1953). An inhibition of 50% is given by 2.2 //moles 



